Implementing the new IASLC/ATS/ERS classification of lung adenocarcinomas: results from international and Chinese cohorts

Lung cancer is the leading cause of cancer death worldwide (1). Over the past decade, the rate of adenocarcinoma (the most frequent subtype of lung cancer) has increased in most countries (2,3). Currently, the single most important factor that determines prognosis for patients with lung adenocarcinomas is tumor-nodal-metastasis stage (4). Lung adenocarcinoma is a heterogeneous tumor with variation in pathological profile. Histologic classifications of lung cancers have been published by the World Health Organization (WHO) in 1967, 1981, 1999, and 2004, and the most recent revision has introduced relevant clinical and genetic information (5). Despite this, there is still limited clinical utility in the 2004 classification of lung adenocarcinomas since more than 90% of adenocarcinomas are classified as a mixed subtype even though they have a variety of clinical outcomes (6-8). Increasing evidence suggests that histologic patterns can identify significant prognostic subsets of patients with lung adenocarcinomas (8-13). Multiple studies have shown that patients with pure lepidic (noninvasive) adenocarcinomas had 100%, 5-year disease-free survival (14-17). Other studies showed that patients with lepidic predominant, minimally invasive (≤5 mm invasion) adenocarcinomas had a near 100% survival (9,10,18). Lepidic predominant invasive tumors also correlate with a favorable prognosis in patients with resected lung adenocarcinomas (19-21). In contrast, the micropapillary pattern has been identified as a poor prognostic factor in patients with lung adenocarcinomas (22,23). To address the advances in the prognostic pathological findings identified over the last decade, a new histologic classification is needed to provide histological subtypes with uniform terminology and diagnostic criteria